Worker Health Study Summaries

Research on long-term exposure

Sterilization of Medical Instruments and Treatment of Spices (Ethylene Oxide)

April 2004

Background of Two Studies

The National Institute for Occupational Safety and Health (NIOSH) conducted two studies to examine the health effects from exposure to ethylene oxide (EtO). EtO is a gas used to sterilize medical instruments and treat spices (among other uses). EtO exposure has been reported in some human and animal studies to be associated with cancers of the blood. EtO has also been reported in some studies to be associated with cancer of the breast in women, but this evidence is less solid than it is for blood cancers at this time.

NIOSH initially completed a mortality study of 18,235 workers exposed to EtO. After that study was completed, in 1993 the results were presented as a poster and sent to each of the 14 study plants. We since have updated the study results by adding 11 years of mortality data. The updated mortality study was done to learn if there were more deaths than would be expected due to cancer or other diseases among workers at these plants. In a second study, we analyzed the incidence (occurrence) of breast cancer among the 7,576 women who had worked at any of the 14 plants for at least one year. Sixty-eight percent of these women (or their next-of-kin) completed a questionnaire about their health.

This NIOSH Fact Sheet discusses what the study results were and what the results may mean to exposed workers. However, it is important to note that the increased risk of diseases discussed in the Fact Sheet refers to workers as a group. We cannot predict the future health of any individual worker.

Women who are interested can obtain more information regarding breast cancer from the American Cancer SocietyExternal (ACS.) The first item, entitled “Guidelines for the Early Detection of Breast Cancer,” is an “over-the-shower” card. It lists ways of finding breast cancer, so that it can be treated as soon as possible. The second item from ACS is a pamphlet entitled, “Breast Cancer: Questions and Answers.” This pamphlet answers questions often asked about breast cancer.

Purpose

To determine if exposure to EtO is related to cancer or other diseases.

Subjects

18,235 men and women exposed to EtO from 14 sterilizer plants around the country. Most of these workers used EtO to sterilize medical supplies and treat spices. These were the largest studies ever conducted on EtO exposure and the risk of disease.

Findings

No overall elevated risk for any type of cancer or other diseases as compared to the general U.S. population.

However, among those workers with very high EtO exposures, (combination of exposure levels and years worked); there was evidence of an elevated risk for blood cancers among men and breast cancers among women.

Conclusions

Persons exposed to very high levels of EtO may be at an increased risk of developing blood cancers among men and breast cancers among women.

Since 1985, when the new OSHA EtO standard went into effect, worker EtO exposures have been significantly lowered, which has reduced the risk of disease.

Why Did NIOSH Do the EtO Studies?

Since the early 1980s, we have been doing research on the chemical ethylene oxide (EtO). Our purpose has been to determine if EtO is related to cancer or other diseases.Animal studies have shown an increase in leukemia and brain cancer. Also, some earlier and much smaller studies of humans who work around EtO found more leukemia, stomach cancer, and cancer of the pancreas than expected.

However, some other studies did not find a cancer increase among workers. Since it was unclear from these studies whether exposure to EtO caused cancer or other diseases, NIOSH did its own studies to look further into this issue.

The 1991 NIOSH Mortality Study of EtO Exposure

In 1991, NIOSH completed its first study of the risk of dying from exposure to EtO.

We call this a mortality study. This type of study is based on causes of death among exposed humans.

The results of the 1991 study showed some evidence of a link between EtO and leukemia and lymphoma (blood cancers) in men (but not in women). However, NIOSH did not consider these results conclusive.

In 1993, NIOSH researchers developed a poster that described the study results. NIOSH sent a poster to each of the 14 plants in the study. However, when the results were posted, many workers may not have been working any longer at the plants.

Two New NIOSH Studies of EtO

The first of the two new studies of EtO, is an update of the earlier 1991 NIOSH mortality study. The results were reported in 2003. We now have added 11 more years of data.

In the second study, we looked at the risk of developing breast cancer among women exposed to EtO. This type of research is called an incidence study.

While mortality studies look at causes of death, incidence studies look at living individuals who actually have a particular disease. In this case, the disease was breast cancer.

The results of the updated EtO mortality study and the results of the EtO breast cancer incidence study are presented in this fact sheet.

The Updated EtO Mortality Study

The NIOSH updated mortality study of EtO is the largest ever to look at the health effects from exposure to EtO. It included 18,235 workers. NIOSH also collected air samples of EtO from the various study plants. Therefore, we could estimate EtO exposures among the workers.

Fourteen plants from 10 companies were included in the study. Most used EtO to sterilize medical supplies and treat spices. Some made sterilizers that used EtO.

EtO Study Subjects

The study group included workers employed at the plants for three months or longer sometime between the early 1940s through the 1980s. Most worked as sterilizer operators, in the sterilizer area, in maintenance, the warehouse, the laboratory, or in other production jobs.

The latest update followed the group through 1998.
The mortality study update was based on three types of records:

Work histories

EtO air samples

Death certificates

Workers did not get a medical examination for this study. Many workers did not know they were included in the study.

Death Rates

First, we calculated the death rates for the whole U.S. population. This gave us the number of deaths we would expect to find among the workers in the mortality study. Then we compared the actual number of deaths and their causes among the EtO-exposed workers in the study to the number of deaths we expected based on the U.S. rates.

If the death rate for any disease was higher in workers than in the general public, then this may have been due to the workers’ EtO exposure.

Leukemia and Lymphoma

The mortality study update found no overall increase in death due to leukemia or lymphoma (cancers of the blood).

However, we did find an elevated risk for blood cancers among men who had received the highest cumulative exposure to EtO. This finding was linked to the total amount of EtO exposure the men had received during their employment at the plants.

The study update, however, showed a smaller elevated risk for blood cancers than was seen in the earlier 1991 NIOSH study.

Nonetheless, the updated study still suggests that EtO in higher amounts may cause blood cancers in men.

Breast Cancer

The study update found no overall increase in death due to breast cancer.

The study did find evidence of an increase in death due to breast cancer among women who had received high exposures to EtO for many years.

Stomach, Brain, and Pancreatic Cancer

We did not find any deaths due to cancer of the stomach, brain, or pancreas beyond what we expected. Thus, we no longer think these cancers are related to EtO exposure. Some earlier studies have found increases in these cancers.

Other Diseases

The death rates for all other diseases were within the expected (normal) range.

The EtO Breast Cancer Incidence Study

The incidence study of breast cancer included 7,576 women who had worked for at least one year at these plants. These women, or their next-of-kin, completed a questionnaire. The questions included information on work history, reproductive history, and family history of breast cancer. Breast cancer exams (mammograms) were not part of this incidence study.

We calculated the occurrence of breast cancer among 10% of the U.S. female population. This gave us the number of women we would expect to develop breast cancer. Then we compared this expected rate to the rate of women in the study who actually developed breast cancer.

If the occurrence of breast cancer was higher among the women in our study compared to that in the general U.S. population, then this may have been due to EtO exposure.

What Did the NIOSH Breast Cancer Incidence Study Find?

The incidence study found no overall increase in breast cancer among the women in the study. However, we did find an increased risk among those with the highest cumulative exposures to EtO. This means that the women with highest amounts of EtO accumulated exposure during their employment at the plants had the greatest risk of developing breast cancer.

We were able to estimate cumulative exposure by calculating the EtO air sample levels and the amount of time women spent doing their various jobs at the plants. The combination of these two factors tells us the cumulative exposure for each worker.

This result supports the breast cancer finding in the EtO mortality study that women exposed to high levels of EtO for many years may be at an increased risk for breast cancer.

Exposure to EtO

Exposure to EtO occurs when the gas is breathed in or when the liquid gets on the skin.

Persons exposed to higher levels of EtO and for longer periods of time may be at a greater risk of developing cancers of the blood (in men) and breast cancer (in women).

Since 1983, NIOSH has recommended that EtO exposure be no higher than 0.1 parts per million (ppm) averaged over 8 hours or 5 ppm averaged over 10 minutes.

Before 1985, companies had to comply with the previous Occupational Safety and Health Administration’s (OSHA) EtO workplace exposure limit of 50 ppm averaged over 8 hours.

Since 1985, companies had to use controls to reduce exposures even more. At that time exposure limits dropped to 1 ppm, which is the most recent EtO exposure limit guideline required by OSHA.

Most workers in our studies were exposed years prior to 1985 when EtO exposures were much higher than they are today. Among the workers in this group, the average exposure to EtO for sterilizer operators from 1976-1985 was 4.3 ppm averaged over 8-hours. The average for other workers was 2.0 ppm.

It is important to keep in mind, however, that our studies look at the risk of diseases among the group as a whole. We cannot predict the risk for any individual.

Furthermore, the much lower EtO level in the workplace since 1985 significantly reduce the likelihood of increased risk of cancers of the blood or the breast among workers exposed to EtO beginning after 1985.

In 1994, the International Agency for Research on Cancer (IARC) classified EtO as a definite cancer-causing agent in humans, although evidence from worker health studies was judged to be limited. Prior to 1994, IARC classified EtO as a probable cancer-causing agent.

Steps To Protect Your Health

You can take steps to protect your health.

Keep your exposure to EtO as low as possible. Handle it as a hazardous substance.

Symptoms

Symptoms of lymphoma may include the following: enlarged gland followed by fever, weight loss, and weakness.

Having any of these symptoms does not necessarily mean you have a serious illness. Other less serious conditions also have these symptoms. However, have your health checked by your doctor to be sure, especially if the symptoms do not go away.

What Are Some Other Health Effects of EtO?

EtO is highly flammable and could cause explosions if not handled properly.

EtO can cause skin or eye irritation, including burns.

At high levels, EtO may affect the nervous system or cause problems such as headache, nausea, muscle weakness, or shortness of breath. At very high exposure levels, EtO is quite hazardous.

The NIOSH studies were not designed to look at reproduction. However, several studies using research animals have looked at those effects of EtO. Some other studies have shown that high levels of EtO affected the sperm and testicles of male animals. EtO also affected the unborn fetus of research animals.

More studies in humans should be done to help clarify these findings.

Breast Cancer: Who is at Risk?

Breast cancer is the most common form of cancer in women and increases:

with age

if you had it before

if your mother, sister, or daughter had breast cancer

if you take estrogen

if you are older at the time of your first pregnancy

if you are exposed to radiation

if you drink alcoholic beverages

The best protection for breast cancer is to detect it as early as possible and treat it promptly.

The following are guidelines from the American Cancer Society for early detection of breast cancer:

Have annual mammograms beginning at age 40.

See your doctor for regular breast exams. Women age 20-39 should have a breast exam every 3 years. Beginning at age 40, women should be tested every year.

Practice monthly breast self-examination. Ask your health care provider to show you the proper way to examine your own breasts.

Any Questions?

If you have any questions or would like a copy of the study reports, please call the NIOSH toll-free number: